This application proposes a series of experimental neuroanatomical studies on the development of muscle spindles in the rat soleus muscle. It has three main objectives: 1) to examine the developmental mechanisms whereby spindles acquire the adult pattern of their sensory and motor neural connections; 2) to determine the role of sensory and motor neurons in the structural and histochemical differentiation of intrafusal fibers; and 3) to explore the mechanisms of the ontogenic effect of sensory neurons on spindle formation. Neural and muscular features of spindles in the soleus muscle will be compared by light and electron microscopy between developing and adult rats. In a complementary study, these features of developing spindles will also be compared between normal controls and animals subjected to experimental deafferentation and exposure to tetrodotoxin. These comparisons will be used to a) determine the temporal sequence of the development of sensory and motor innervation to spindles; b) establish whether transient, immature patterns of innervation procede the emergence of the adult pattern of neural connections of spindles; c) determine whether the motor innervation can direct the differentiation of developing spindles in the absence of sensory innervation; and d) explore whether nerve activity could mediate the ontogenetic effects of sensory axons on spindle formation. The proposed study aims at providing new insights into the process of formation and differentiation of mammalian muscle spindles. It will also explore nerve-muscle interactions during the development of a highly specialized class of muscle fibers - the intrafusal fibers of muscle spindles.